Identification of a bovine surface antigen uniquely expressed on CD4−CD8− T cell receptor γ/δ+ T lymphocytes

Clevers, Hans; MacHugh, Niall D.; Bensaïd, Albert; Dunlap, Sabrina; Baldwin, Cynthia L.; Kaushal, A.; Iams, Keith P.; Howard, Chris; Morrison, W. Ivan

doi:10.1002/eji.1830200415

Cited by 193 publications

(102 citation statements)

References 40 publications

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“…The involvement of CD8 T cells was inferred from ablation of cytotoxicity following depletion of CD8 T cells by antibody-and complementmediated lysis. Since CD8 is also known to be expressed on bovine NK cells and gd T cells [36,37], which can exhibit cytotoxic activity, the attribution of the cytotoxicity measured in these studies to classical CD8 T cells remains open to question. Nevertheless, it is possible that CD8 T cells specific for additional antigens, including the glycoproteins, were present at low frequency in our T-cell lines, but were not detected by our screening method.…”

Section: Discussionmentioning

confidence: 99%

Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

Hart

MacHugh

Sheldrake

et al. 2017

Journal of General Virology

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In common with other herpes viruses, bovine herpes virus 1 (BHV-1) induces strong virus-specific CD8 T-cell responses. However, there is a paucity of information on the antigenic specificity of the responding T-cells. The development of a system to generate virus-specific CD8 T-cell lines from BHV-1-immune cattle, employing Theileria-transformed cell lines for antigen presentation, has enabled us to address this issue. Use of this system allowed the study to screen for CD8 T-cell antigens that are efficiently presented on the surface of virus-infected cells. Screening of a panel of 16 candidate viral gene products with CD8 T-cell lines from 3 BHV-1-immune cattle of defined MHC genotypes identified 4 antigens, including 3 immediate early (IE) gene products (ICP4, ICP22 and Circ) and a tegument protein (UL49). Identification of the MHC restriction specificities revealed that the antigens were presented by two or three class I MHC alleles in each animal. Six CD8 T-cell epitopes were identified in the three IE proteins by screening of synthetic peptides. Use of an algorithm (NetMHCpan) that predicts the peptide-binding characteristics of restricting MHC alleles confirmed and, in some cases refined, the identity of the epitopes. Analyses of the epitope specificity of the CD8 T-cell lines showed that a large component of the response is directed against these IE epitopes. The results indicate that these IE gene products are dominant targets of the CD8 T-cell response in BHV-I-immune cattle and hence are prime-candidate antigens for the generation of a subunit vaccine.

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Section: Discussionmentioning

confidence: 99%

Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

Hart

MacHugh

Sheldrake

et al. 2017

Journal of General Virology

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“…This is in sharp contrast with porcine CD2 2 gd T cells, which are numerous and preferentially reside in the blood. High occurrence of CD2 2 gd T cells is not unique to pigs but also for other members of gd-high species such as sheep (28,29), cattle (30), and birds (31). These findings together support the idea that CD2 2 gd T cells are a specific lineage, and this lineage is missing in the blood of humans and mice.…”

Section: Discussionmentioning

confidence: 99%

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Štěpánová

Šinkora

2013

The Journal of Immunology

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Porcine γδ T cells have two levels of TCRγδ expression. Whereas TCRγδmed cells are mostly CD2+CD8− and CD2+CD8+, TCRγδhi cells are highly enriched for CD2−CD8−. This distribution is independent of bacterial colonization and it is already established in the thymus prior to export of γδ cells to the periphery. Sorting and cultivation experiments revealed that CD2−CD8− γδ cells are unable to acquire CD2 and CD8, whereas CD2+ subsets can gain or loose CD8. There is also differential susceptibility for proliferation between CD2+ and CD2− γδ cells. Although CD2−CD8− almost do not proliferate, proliferation of CD2+CD8− and CD2+CD8+ is substantial. Population of CD2− γδ cells is also absent in CD1+ immature thymocytes. Additionally, subpopulations of CD2+ and CD2− γδ cells in the thymus differ in expression of auxiliary surface molecules such as CD25, CD45RA/RC, and MHC class II. Moreover, TCRγδhi cells can generate TCRγδmed cells but never the opposite. The only exception is the thymus, where a few TCRγδmed cells can be induced to TCRγδhi but only under IL-2 influence. The repertoire of TCRδ is polyclonal in all subsets, indicating that there is the same extent of diversification and equal capability of immune responses. Results collectively indicate that CD2 expression determines two lineages of γδ cells that differ in many aspects. Because CD2− γδ cells are missing in the blood of humans and mice but are obvious in other members of γδ-high species such as ruminants and birds, our findings support the idea that circulating CD2− γδ T cells are a specific lineage.

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“…The lysate was cleared by centrifugation at 13 000g for 10 min and then incubated with 20 mL Protein G PLUS-Agarose beads (Santa Cruz Biotech, Santa Cruz, CA, USA) at 41C with constant rotation for 30 min. The supernatant was obtained by centrifugation at 13 000g for 1 min, collected, and incubated with 1 or 2 mg of various antibodies individually at 41C under constant rotation for 3 h. Antibodies were IL-A29 [45], which is a pan-specific mAb reactive with the majority of WC1 molecules, control IgG1 (Southern Biotech, Birmingham, AL, USA), anti-lyn (Serotec), anti-blk (Serotec), or anti-src (Upstate, Billerica, MA, USA). Following this, 30 mL Protein G PLUS-Agarose beads or Protein A-sepharose beads (GE Health Care, Piscataway, NJ, USA) was added and rotated for another 1 h. The immunocomplexes were washed three times with cold lysis buffer.…”

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Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

et al. 2009

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Workshop cluster 1 (WC1) molecules are transmembrane glycoproteins uniquely expressed by cd T cells. They belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family, which is divided on the basis of antibody reactivity, into three groups, WC1.1, WC1.2, and WC1.3. The potential role of WC1 as a co-stimulatory molecule for the cd TCR is suggested by the presence of several tyrosinebased motifs in their intracellular domains. In this study, we found that WC1 was constitutively phosphorylated in ex vivo bovine cd T cells and associated with src family tyrosine kinases. Crosslinking of WC1 molecules resulted in an increase in WC1 phosphorylation and co-crosslinking of WC1 and cd TCR together prolonged WC1 phosphorylation. We identified the second tyrosine residue as the primary phosphorylation target in WC1.1 and WC1.2 intracellular sequences in both in vitro and in vivo assays. The cytoplasmic tails of WC1.1 and WC1.2 were phosphorylated on serine and PKC activity was required for PMA-induced endocytosis of WC1.1 or WC1.2. We found that phosphorylation of the second tyrosine in the WC1 cytoplasmic domain was required for the WC1-mediated potentiation of TCR-induced T-cell proliferation, suggesting that WC1 acts as a co-stimulatory molecule for cd TCR.Key words: Bovine . Cell surface molecules . gd T cells . Signal transduction IntroductionIn adult chickens, ruminants and pigs, unlike in mice and humans, gd T cells can constitute 30% of total PBMC [1]. A majority of these gd T cells in ruminants bear the glycoprotein lineage marker Workshop cluster 1 (WC1) on their surface. Based on the profiles of their gene expression, WC1 1 gd T cells of cattle represent the inflammatory population, whereas WC1 À gd T cells are regulatory cells [2,3]. WC1, a member of the scavenger receptor cysteine-rich (SRCR) superfamily, is categorized into group B along with CD5, CD6, and CD163, based on the organization of cysteine residues in its extracellular SRCR domains [4]. Like the SRCR family member SpSRCR, which is expressed in the immune cells of the purple sea urchin [5], WC1 molecules are products of a large gene family, and thus have the potential to increase the diversity of immune responses independently of the adaptive immune response receptor, i.e. the TCR.Bovine gd T cells express at least three known variants, WC1.1, WC1.2, and WC1.3, which are defined by antibodies recognizing unknown epitopes on their SRCR domains [6]. WC1.1 and WC1.2 are expressed on two mostly non-overlapping subsets of bovine gd T cells, and WC1.3 is expressed on a small 254subpopulation of WC1.1 1 cells. Cytokine production and cellular proliferation in response to stimulation vary according to the forms of WC1 expressed by gd T cells [7]. Ex vivo WC1.1 1 gd T cells, but not WC1.2 1 gd T cells, proliferate well to the gd T-cell antigens of Leptospira, and produce IFN-g in response to either antigen or 8].The correlation of the expression of a variable WC1 gene product with a cellular immune response to antigen su...

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Identification of a bovine surface antigen uniquely expressed on CD4⁻CD8⁻ T cell receptor γ/δ⁺ T lymphocytes

Cited by 193 publications

References 40 publications

Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

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